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Metabolic Brain Disease

, Volume 31, Issue 6, pp 1391–1403 | Cite as

Delayed bradykinin postconditioning modulates intrinsic neuroprotective enzyme expression in the rat CA1 region after cerebral ischemia: a proteomic study

  • Miroslava NemethovaEmail author
  • Ivan Talian
  • Viera Danielisova
  • Sona Tkacikova
  • Petra Bonova
  • Peter Bober
  • Milina Matiasova
  • Jan Sabo
  • Jozef Burda
Original Article

Abstract

Pyramidal cells in the CA1 brain region exhibit an ischemic tolerance after delayed postconditioning; therefore, this approach seems to be a promising neuroprotective procedure in cerebral postischemic injury improvement. However, little is known about the effect of postconditioning on protein expression patterns in the brain, especially in the affected hippocampal neurons after global cerebral ischemia. This study is focused on the examination of the ischemia-vulnerable CA1 neuronal layer and on the acquisition of protection from delayed neuronal death after ischemia. Ischemic-reperfusion injury was induced in Wistar rats and bradykinin was applied 2 days after the ischemic insult in an attempt to overcome delayed cell death. Analysis of complex peptide CA1 samples was performed by automated two dimensional liquid chromatography (2D-LC) fractionation coupled to tandem matrix assisted laser desorption/ionization time-of-flight (MALDI TOF/TOF) mass spectrometry instrumentation. We devoted our attention to differences in protein expression mapping in ischemic injured CA1 neurons in comparison with equally affected neurons, but with bradykinin application. Proteomic analysis identified several proteins occurring only after postconditioning and control, which could have a potentially neuroprotective influence on ischemic injured neurons. Among them, the prominent position occupies a regulator of glutamate level aspartate transaminase AATC, a scavenger of glutamate in brain neuroprotection after ischemia-reperfusion. We identified this enzyme in controls and after postconditioning, but AATC presence was not detected in the ischemic injured CA1 region. This finding was confirmed by two-dimensional differential electrophoresis followed by MALDI-TOF/TOF MS identification. Results suggest that bradykinin as delayed postconditioning may be associated with modulation of protein expression after ischemic injury and thus this procedure can be involved in neuroprotective metabolic pathways.

Keywords

Cerebral ischemia Rat Hippocampus Postconditioning MALDI Proteomics 

Notes

Acknowledgments

We are indebted to Dana Jurušová for her technical assistance. We gratefully acknowledge financial support as follows. This study is the result of implementation of the project: “New possibilities of preservation of neurons in the process of delayed neuronal death by nonspecific stressors”; supported by the European Research & Development Operational Programme Funded by the ERDF - ITMS 26220220043 and by grants from the Slovak Scientific Grant Agency VEGA 2/0012/15 and 2/0045/15.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed

Supplementary material

11011_2016_9859_MOESM1_ESM.pdf (173 kb)
ESM 1 (PDF 173 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Institute of Neurobiology, SASKosiceSlovakia
  2. 2.Department of Medical and Clinical Biophysics, Faculty of MedicineP. J. Safarik UniversityKosiceSlovakia

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